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Down syndrome (DS) occurs with triplication of human chromosome 21 and is associated with deviations in cortical development evidenced by simplified gyral appearance and reduced cortical surface area. Radial glia are neuronal and glial progenitors that also create a scaffolding structure essential for migrating neurons to reach cortical targets and therefore play a critical role in cortical development. The aim of this study was to characterise radial glial expression pattern and morphology in the frontal lobe of the developing human fetal brain with DS and age-matched controls. Secondly, we investigated whether microstructural information from in vivo magnetic resonance imaging (MRI) could reflect histological findings from human brain tissue samples. Immunohistochemistry was performed on paraffin-embedded human post-mortem brain tissue from nine fetuses and neonates with DS (15-39 gestational weeks (GW)) and nine euploid age-matched brains (18-39 GW). Radial glia markers CRYAB, HOPX, SOX2, GFAP and Vimentin were assessed in the Ventricular Zone, Subventricular Zone and Intermediate Zone. In vivo diffusion MRI was used to assess microstructure in these regions in one DS (21 GW) and one control (22 GW) fetal brain. We found a significant reduction in radial glial progenitor SOX2 and subtle deviations in radial glia expression (GFAP and Vimentin) prior to 24 GW in DS. In vivo, fetal MRI demonstrates underlying radial projections consistent with immunohistopathology. Radial glial alterations may contribute to the subsequent simplified gyral patterns and decreased cortical volumes observed in the DS brain. Recent advances in fetal MRI acquisition and analysis could provide non-invasive imaging-based biomarkers of early developmental deviations.

Bestrophin-3, a potential candidate for a calcium-activated chloride channel, recently was suggested to have cell-protective functions. We studied the expression and alternative splicing of bestrophin-3 in neonatal mouse brain and after hypoxic-ischemic (HI) injury and in human neonatal brain samples. HI brain injury was induced in 9-day old mice by unilateral permanent common carotid artery occlusion in combination with exposure to 10% oxygen for 50 min. Endoplasmic reticulum stress was induced by thapsigargin treatment in primary culture of mouse brain astrocytes. We also investigated expression of bestrophin-3 protein in a sample of human neonatal brain tissue. Bestrophin-3 protein expression was detected with immunohistochemical methods and western blot; mRNA expression and splicing were analyzed by RT-PCR. HI induced a brain tissue infarct and a pronounced increase in the endoplasmic reticulum-associated marker CHOP. Three days after HI a population of astrocytes co-expressed bestrophin-3 and nestin in a penumbra-like area of the injured hemisphere. However, total levels of Bestrophin-3 protein in mouse cortex were reduced after injury. Mouse astrocytes in primary culture also expressed bestrophin-3 protein, the amount of which was reduced by endoplasmic reticulum stress. Bestrophin-3 protein was detected in astrocytes in the hippocampal region of the human neonatal brain which had patchy white matter gliosis and neuronal loss in the Sommer's sector of the Ammon's horn (CA1). Analysis of bestrophin-3 mRNA in mouse brain with and without injury showed the presence of two truncated spliced variants, but no full-length mRNA. Total amount of bestrophin-3 mRNA increased after HI, but showed only minor injury-related change. However, the splice variants of bestrophin-3 mRNA were differentially regulated after HI depending on the presence of tissue injury. Our results show that bestrophin-3 is expressed in neonatal mouse brain after injury and in the human neonatal brain with pathology. In mouse brain bestrophin-3 protein is upregulated in a specific astrocyte population after injury and is co-expressed with nestin. Splice variants of bestrophin-3 mRNA respond differently to HI, which might indicate their different roles in tissue injury.

Toll-like receptor-3 (TLR3) has been identified in a variety of intracellular structures (e.g. endosomes and endoplasmic reticulum); it detects viral molecular patterns and damage-associated molecular patterns. We hypothesized that, after white matter injury (WMI) has occurred, localization and activation of TLR3 are altered in gray matter structures in response to damage-associated molecular patterns and activated glia. Therefore, we investigated the subcellular localization of TLR3 and its downstream signaling pathway in postmortem brain sections from preterm infants with and without WMI (7 patients each). We assessed astroglia (glial fibrillary acidic protein-positive), microglia (ionized calcium-binding adaptor molecule-1-positive), and neuronal populations in 3 regions of the thalamus and in the posterior limb of the internal capsule and analyzed TLR3 messenger RNA and protein expression in the ventral lateral posterior thalamic region, an area associated with impaired motor function. We also assessed TLR3 colocalization with late endosomes (lysosome-associated membrane protein-1) and phagosomal compartments in this region. Glial fibrillary acidic protein, ionized calcium-binding adaptor molecule-1, and TLR3 immunoreactivity and messenger RNA expression were increased in cases with WMI compared with controls. In ventral lateral posterior neurons, TLR3 was colocalized with the endoplasmic reticulum and the autophagosome, suggesting that autophagy may be a stress response associated with WMI. Thus, alterations in TLR3 expression in WMI may be an underlying molecular mechanism associated with impaired development in preterm infants.

Neoaortic insufficiency is not uncommon after the arterial switch operation (ASO) for d-Transposition, yet surgery is rarely required. In a patient with worsening neoaortic regurgitation post-arterial switch and ventricular septal defect (VSD) closure, we performed a successful "switch back" operation with documented aortic valve competence on discharge echocardiography. However, recurrent severe aortic insufficiency required valve replacement, and histopathology of the excised valve indicated abnormal leaflet/vascular wall structure. We question whether the switch back operation is a viable option for neoaortic insufficiency after an ASO in patients with previous d-Transposition and VSD, when the native pulmonary valve may have structural deficiencies., (© The Author(s) 2014.)

Deletions of the long arm of chromosome 2 are rare. Few cases of interstitial deletions of the 2q33q35 region have been reported. Individuals with deletions in this region have growth retardation, psychomotor retardation, micrognathia, microcephaly, and apparently low-set ears. We describe a female fetus with a de novo deletion of 2q33.2 to q35 with delayed gyral formation with widespread neuronal heterotopia of the white matter, small cerebellum, esophageal atresia, laryngeal stenosis, micrognathia, and intrauterine growth retardation. With the use of karyotyping and high-resolution array comparative genomic hybridization the boundaries and gene content of the deletion were identified. Our aim was to determine whether a candidate gene for the brain phenotype was present in the deletion. By this means and based on literature we pinpointed the microtubule associated gene MAP2 as a candidate for the brain anomalies., (© 2013 Wiley Periodicals, Inc.)

An antenatally diagnosed case of a left congenital diaphragmatic hernia is reported. The diaphragmatic eventration hernia sac consisted of a sheet of ectopic liver tissue in continuity with a hypoplastic left lobe which formed the medial anterior and posterior walls of the hernia is presented. The operative management of this combination of defects has not previously been described in English literature. Embryological considerations, limitations of accurate preoperative diagnosis, technical challenge in the operative repair of the defect and need for drainage is discussed.

Background: The periventricular white matter (PVWM) of the immature preterm brain is selectively vulnerable to a spectrum of injury. Although essential for normal brain development, the presence of resident microglia may exacerbate PVWM injury., Methods: We used immunohistochemistry to investigate microglia profile in human preterm noninjured control brains and in brains with evidence of germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH), with median gestational age (GA) of 24.1 and 25.4 wk, respectively., Results: The number of microglia in the PVWM was higher than the other brain regions in both the control and GMH/IVH groups. Microglial density increased further in the PVWM of GMH/IVH brains, regardless of hemorrhage severity and despite normal macroscopic and imaging appearances to the PVWM. This was due to an increase in activated Iba1/CD68- and not Iba/CD45-immunopositive microglia. However, there were very few CD68/Ki67 colocalized cells, suggesting that the source of this increase may be due to a quick transformation of CD45-immunopositive hematopoietic microglia into CD68-immunopositive microglia. There was also increased apoptosis in the PVWM of all cases of GMH/IVH, with axonal injury and increased tumor necrosis factor-α (TNF-α) expression evident in the most severe cases., Conclusion: Isolated GMH/IVH may influence ongoing brain development, with a significant role played by microglial activation.

The 40-fold increase in childhood megakaryocyte-erythroid and B-cell leukemia in Down syndrome implicates trisomy 21 (T21) in perturbing fetal hematopoiesis. Here, we show that compared with primary disomic controls, primary T21 fetal liver (FL) hematopoietic stem cells (HSC) and megakaryocyte-erythroid progenitors are markedly increased, whereas granulocyte-macrophage progenitors are reduced. Commensurately, HSC and megakaryocyte-erythroid progenitors show higher clonogenicity, with increased megakaryocyte, megakaryocyte-erythroid, and replatable blast colonies. Biased megakaryocyte-erythroid-primed gene expression was detected as early as the HSC compartment. In lymphopoiesis, T21 FL lymphoid-primed multipotential progenitors and early lymphoid progenitor numbers are maintained, but there was a 10-fold reduction in committed PreproB-lymphoid progenitors and the functional B-cell potential of HSC and early lymphoid progenitor is severely impaired, in tandem with reduced early lymphoid gene expression. The same pattern was seen in all T21 FL samples and no samples had GATA1 mutations. Therefore, T21 itself causes multiple distinct defects in FL myelo- and lymphopoiesis.

Antenatal closure of the ductus arteriosus has been speculated, but rarely reported, as a cause of hydrops fetalis. The purpose of this prospective autopsy study was to find the incidence of antenatal closure of the ductus arteriosus and hydrops fetalis in a high-risk obstetric population and to find associated factors that might give clues to the cause of antenatal closure of the ductus arteriosus. Antenatal closure of the ductus arteriosus had to be stringently sought by in situ examination. Fifteen stillborns with antenatal closure of the ductus arteriosus were found in 684 perinatal autopsies (2.2%), including 511 stillborns (2.9%). All 15 stillborns with antenatal closure of the ductus arteriosus also had hydrops fetalis and accounted for 35% of the 43 stillborns with hydrops fetalis. Antenatal closure of the ductus arteriosus in these 15 stillborns was not associated with maternal aspirin use but was associated with a myriad of factors, including intrauterine infection (60%), umbilical cord abnormalities (67%), and retroplacental hemorrhage (87%), that can cause hypoxic-ischemic stress.

Objectives: We reviewed all cases with fetal skeletal dysplasia and correlated the accuracy of prenatal diagnoses with the final post-mortem, radiological, or molecular diagnoses. The accuracy of prenatal prediction of lethality was also reviewed., Methods: All cases of fetal skeletal dysplasia referred between October 2002 and August 2010 were reviewed. Perinatal outcome, the accuracy of prenatal diagnosis, and prediction of lethality were ascertained. Lethality was suspected when significant thoracic narrowing, severe micromelia, multiple fractures, or long bone bowing was present., Results: There were 40 cases of skeletal dysplasia. Thirty-nine (97.5%) were singletons and one (2.5%) was a dichorionic twin pregnancy. Twenty-eight (70%) pregnancies were terminated, five (12.5%) were stillborn, and only seven (17.5%) cases were live born. A final diagnosis was established in 28 (70%) cases. In 29 cases with a presumptive prenatal diagnosis, this was confirmed in 23 (79.3%) cases postnatally. Lethality was predicted with 100% certainty., Conclusion: We report higher prenatal/postnatal concordance rates in this series. A precise prenatal diagnosis is frequently difficult and often inaccurate. Prediction of lethality is much easier and often possible with accuracy. Parents need to be aware that the outcome of many skeletal dysplasias is poor., (Copyright © 2011 John Wiley & Sons, Ltd.)

To evaluate neurological effects of terbutaline, rats were injected with saline, terbutaline (Sigma or American Pharmaceutical Partners (APP™)) at 0.5 mg/kg-d or 10 mg/kg-d between postnatal days (PND) 2-5 or 11-14. Brains collected 24 h after last injection were used to determine corpus-callosum thickness, Purkinje cell and neuronal number in the cerebellum. Ambulation, distance traveled, resting time and time on rotarod were analyzed. Terbutaline (both doses/grades at PND 11-14) decreased corpus-callosum thickness. Ambulation time was significantly decreased in the 10 mg/kg-d (Sigma) and 0.5 mg/kg-d of terbutaline (APP™) (PND 2-5) juvenile-rats and 10 mg/kg-d-Sigma adult-rats, 0.5 mg/kg-d APP™ (PND 11-14) adult-rats. Resting time was increased in both doses of APP™ (PND 2-5) in juvenile-rats, 10 mg/kg-d Sigma adult-rats. 10 mg/kg-d-Sigma (PND 2-5) decreased distance traveled in adult-rats. 0.5 mg/kg-d-Sigma (PND 2-5 and PND 11-14) decreased the time spent on rotarod (30 RPM) in adult-rats. Sigma terbutaline Sigma had 2× as much free base compared to APP™. In conclusion, APP™ terbutaline did not have a deleterious effect on the developing rat brain., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Fetal cells trafficking into maternal blood during pregnancy engraft tissues and persist for decades in marrow and bone. While persistent fetal cells were initially implicated in autoimmune disease, animal studies suggest that microchimeric fetal cells play a broader role in response to tissue injury. This study investigated whether fetal cells participate in tissue repair after human pregnancy. Specimens were obtained from women undergoing surgery for suspected lung cancer. Y-fluorescence in-situ hybridization was performed on paraffin-embedded sections, with the investigator blinded to medical histories. Male cells were identified in lung/thymus tissue from all women with known male pregnancies, but not in those without sons. The frequency of male microchimeric cells was seven-fold greater in lung/thymus tissues than marrow and was two-fold greater than normal bone from the same women. Nested-polymerase chain reaction for sex determining region Y confirmed male DNA in tissues. Male cells in lung were clustered in tumour rather than surrounding healthy tissues. In conclusion, male presumed-fetal cells were identified in pathological post-reproductive tissues, where they were more likely to be located in diseased tissues at several-fold higher frequency than normal tissues. It is suggested that fetal cells are present at sites of tissue injury and may be stem cells, either recruited from marrow or having proliferated locally.

Background: Traditionally, sickle cell trait has not been associated with a higher risk of fetal death, but we noted several, which led us to assess all such pregnancies., Methods: In this retrospective study, 131 patients with sickle cell trait were analyzed over a two-year period. The Institutional Review Board approved the collection of deidentified data., Results: Subjects were African-American with an average age of 23.9 years, and average gestational age at delivery of 30.1 weeks. There were 10 (8.13%) intrauterine fetal deaths (IUFDs), and one neonatal death. Ascending amniotic fluid infection was noted in 50% and 92% meconium histocytes. All placentas had sickling in the intervillous space and the decidual vessels., Conclusions: Sickling in the decidual vessels and poor placental perfusion may play a role in pregnancy loss in excess of what has previously been reported. A cohort control study appears to be in order., Narrative: Pregnant women with sickle cell trait are thought not to have increased maternal or fetal mortality/morbidity. Over a two year period, we studied 131 women with this hemoglobinopathy and found that 10.6% had intrauterine growth retardation (IUGR), 8.4% preterm premature rupture of the membranes, 8.1% intrauterine fetal demise (n = 10) at most occurring at 16 to 24 weeks, and one neonatal death. Amniotic fluid infection was noted in 50%, and meconium histocytes indicating intrauterine hypoxia were noted, as was unsuspected sickling in the placental vasculature. Based on this case series, sickle cell trait may not be as benign for the fetus as was previously thought.

Objective: The purpose of this study was to evaluate the obstetric outcomes and pathologic findings in women with sickle cell trait., Study Design: In this retrospective case control study, pregnant women with sickle cell trait were studied over a 4-year period (2001-2005). The women who were delivered at > 16 weeks of gestation were compared with a cohort group of subjects with normal hemoglobin levels, and the placentas were sent for pathologic evaluation., Results: A total of 180 pregnancies were studied with a like number of control patients. Subjects who had sickle cell trait demonstrated shorter average duration of pregnancy (233 +/- 45 days vs 255 +/- 34 days; P < .001) and lower birth weight (2114 +/- 1093 g vs 2672 +/- 942 g; P < .001). The rate of fetal death was significantly higher among study group patients (3.5% vs 9.7%; P = .015) when compared with the control group. Additionally, in study women, acute ascending amniotic infection and meconium histiocytosis were noted much more frequently. Sickling in the intervillous space and decidual vessels that were not associated with artifactual change was also found among patients sickle cell trait., Conclusion: Patients with sickle cell trait appear to be at increased risk for fetal loss compared with women with normal hemoglobin levels, and placental abnormalities may play a causal role.

Colonic polyps are common both in adults and children; however, the malignant potential varies according to the type of polyp. Most childhood polyps are solitary juvenile polyps, which have negligible malignant potential. Chicken-skin mucosa (CSM) is an endoscopic finding initially described associated with adenomatous polyps and adenocarcinoma, suggesting a preneoplastic lesion. Subsequently, CSM was described in association with juvenile polyps, suggesting that this mucosal finding is not a precursor to dysplasia. To determine whether CSM represents a preneoplastic lesion, we studied endoscopic colonic mucosal biopsies for markers of cell replication (Ki-67) and malignant transformation (p53) in mucosal biopsies of CSM, normal colonic tissue, tubular adenomas, and adenocarcinomas. Samples were subjected to immunostaining for the presence of Ki-67 and p53. The degree of Ki-67-positive staining cells was similar for CSM and normal colonic tissue, whereas there was significantly increased staining for both tubular adenomas and adenocarcinomas. There was no evidence of p53 staining in CSM and normal colonic mucosa, whereas there was varying degrees of staining in tubular adenomas and adenocarcinomas. The association of CSM with benign juvenile polyps and the absence of histologic markers for increased replication and malignant transformation support the notion that this endoscopic finding is not preneoplastic. Rather, CSM arises in proximity to polyps of all histologic types because of local mucosal damage.

Benign müllerian papilloma of the female reproductive tract is a rare childhood tumor that can easily be mistaken by those unfamiliar with the entity for botryoid rhabdomyosarcoma. Ultrastructural findings have been mentioned only in two individual case reports, and these both were issued many years ago. The aim of this update is to familiarize the reader with the clinical, light, and electron microscopic features associated with this distinctive entity, and thereby hopefully preclude the risk of making a serious diagnostic error. Two cases are illustrated, one very typical in its presentation and the other less so.

Objective: The purpose of this study was to test the hypothesis that interleukin-10 can prevent white matter injury in neonatal rats that are born to infected dams., Study Design: Timed pregnant rats (day 17) were assigned to the following treatment groups: (1) saline control (n = 5 rats), (2) Escherichia coli- infected (n = 10 rats), and (3) E coli + interleukin-10 (n = 5 rats). E coli was administered at a titer of 1 x 10(7) colony-forming units by intrauterine inoculation just above the cervix at the bifurcation of the uterine horns. Rat interleukin-10 was administered intravenously at a dose of 1 microg/kg of body weight. After delivery, the pups were maintained with dams until day 8, at which time they were placed under general anesthesia and perfused with saline solution followed by 10% paraformaldehyde. The brains were removed, placed in 30% sucrose solution, and then frozen at -20 degrees C until the preparation of the frozen sections. Standard hematoxylin/eosin staining was performed, and the brains were evaluated for matter necrosis, apoptotic cells, and ventricular swelling., Results: In pups that were born to infected dams, 11 of 38 pups (29%) displayed symmetric lesions around the lateral ventricles. These lesions were characterized by marked looseness/edema of the neuropil, foamy-appearing histiocytes, and granular neuropil breakdown. None of the pups (n = 17) that were born to interleukin-10-treated infected dams displayed this pattern of severe white matter injury., Conclusion: These results suggest that maternal interleukin-10 therapy could provide neuroprotection for infants who are born to mothers with intrauterine infection.

Pediatric hepatic angiosarcoma (PHAS) is a rare tumor, which usually presents as a rapid enlargement of the liver. To date, surgery, chemotherapy, and radiotherapy have not improved the poor prognosis of PHAS with only three survivors reported. The histology of PHAS is distinct from adult angiosarcoma, because PHAS displays hypercellular whorls of sarcomatous cells, or "kaposiform" spindle cells, in addition to the general features of angiosarcoma. We report a case of PHAS that was treated with vascular ablation, chemotherapy, and liver transplantation. Lung metastases occurred 14 months posttransplant.

The authors present an unusual manifestation of neuroblastoma in a young child: upper gastrointestinal bleeding due to erosion of the tumor into the stomach. Included are reviews of gastrointestinal manifestations of neuroblastoma and gastric tumors in children.

Background: Renal cell carcinoma (RCC) is rare in children and comprises only 1-3% of all pediatric primary renal tumors. Recently, several case reports have described RCC developing in patients previously treated for advanced stage neuroblastoma (NB)., Methods and Results: Our experience with four patients treated for advanced stage NB during early childhood who developed RCC later in life are added to 14 others in the literature., Conclusion: These patients and our review of the literature suggest an association between RCC and NB that warrants further study.

Background: Cytogenetic analysis in certain tumors is a vital part of classification and assignment of prognosis. Few studies have examined the value of cytogenetic analysis in pediatric brain tumors. This is especially true of low-grade astrocytomas (LGA) of childhood. This study examines the correlation between cytogenetic abnormalities and survival in children with low-grade astrocytomas. The literature on adults with LGA suggest better survival for those whose tumors have normal cytogenetics compared to those with abnormal. We hypothesized this would also be true of children with low-grade astrocytomas., Procedure: A retrospective study was performed of children presenting between 1980 and 1998 to The Children's Hospital, Denver, who had LGA and on whose tumors informative cytogenetics had obtained., Results: One hundred and forty-nine children were diagnosed with histologically proven LGA. Twenty-nine had successful cytogenetic analysis. One or more chromosomal abnormalities were observed in eight tumors while normal karyotypes were observed in 21 tumors. Actuarial progression-free survival at 5 years was 87.5% for the eight children with abnormal cytogenetics and 43% for those with normal (P=0.56). Overall survival at 5 years was 83% for those with abnormal cytogenetics and 78% for those with normal (P=0.8). The differences in progression-free survival and overall survival between these two groups were not significant. Those children with WHO Grade I tumors had significantly superior progression-free and overall survival than those with Grade II tumors., Conclusions: It appears unlikely that, for children with LGA, those with normal cytogenetics have a better prognosis than those with abnormal. Histologic grade is a better predictor of outcome than cytogenetics., (Copyright 2002 Wiley-Liss, Inc.)

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.

Rhabdoid phenotypic change has been described in a number of different neoplasms from diverse organ sites. These tumors share common light and electron-microscopic features, display a polyphenotypic immunohistochemical profile and often show cytogenetic abnormalities of chromosome 22. In the central nervous system (CNS), most rhabdoid tumors occur in the posterior fossa of very young children and are associated with a primitive neuroectodermal tumor (PNET) component and are designated atypical teratoid/rhabdoid tumors. Infrequently, other rhabdoid tumors of the CNS have been described, including rhabdoid meningiomas and malignant rhabdoid tumors of uncertain histogenesis. Several examples of conventional gliomas displaying significant areas with rhabdoid morphology were also presented in an abstract by Kepes and Moral [1991], although never published in final manuscript form. We now detail the case of an 18-year-old male with an aggressive, supratentorial CNS rhabdoid tumor that was associated with an epithelioid glioblastoma and apparently arose from areas of low-grade glioma. The rhabdoid tumor component was present in the original tumor but became more predominant with each of 3 successive resections. No areas of PNET were identified. Electron microscopy and immunohistochemistry showed features classic for rhabdoid tumors and cytogenetic studies demonstrated multiple tumor clones with monosomy 22. This case documents progressive rhabdoid transformation of a glioma, expands the spectrum of CNS tumor types that can display a rhabdoid phenotype and highlights the diagnostic and therapeutic challenges with this type of tumor.

Five of six poorly differentiated choroid plexus carcinomas identified at our institution contained cells displaying a rhabdoid phenotype. Immunoperoxidase stains showed focal positivity for cytokeratin, epithelial membrane antigen, glial fibrillary acidic protein, S100, and vimentin. The MIB-1 proliferative index ranged from 7.0% to 27.1%. All six tumors were p53 positive. Only the one child with Li-Fraumeni syndrome had a p53 germline mutation. Electron microscopy verified choroid plexus differentiation and the co-existence of rhabdoid cells. Of the five studied, four had deletions of chromosome 22 [three with monosomy 22 and one with del(22)(q12)]. Thus, there was a phenotypic and genotypic overlap between choroid plexus carcinomas and rhabdoid tumors.

We present a case of plexiform neurofibroma involving the retroperitoneum, mesentery, and liver in a 5-year-old boy who underwent evaluation for extent of a palpable left neck mass. The mass had intrathoracic extension with great vessel encasement and extension into the abdomen. Abdominal CT revealed a diffuse low-attenuation non-enhancing mass encasing the retroperitoneal vessels with serpiginous extension into the liver along the portal vein. This spread pattern of plexiform neurofibroma is an unusual manifestation of neurofibromatosis in a young child.

We report a case of an ectopic, extraspinal meningioma that appeared as a midline interscapular mass in a 13-year-old girl. The tumor involved the T-2 and T-3 spinous processes, but was dorsal to the lamina and was entirely extrinsic to the spinal canal. Large amounts of tumoral calcification and reactive hyperostosis were present, radiologically mimicking an osteogenic sarcoma.

Traditional methods of reconstructing full-thickness urethral defects have employed a cutaneous component utilized to replace the lining of the urethra. These methods have failed to take advantage of the regenerative ability of urethral epithelium. This epithelium is capable of regenerating, eliminating the need for urethral lining reconstruction. Muscle flap reconstruction provides an environment that allows for complete regeneration of the urethral epithelium. A 56-year-old male presented with a 12-cm defect of the bulbous and penile urethra involving 180 degrees of the urethral circumference secondary to Fournier's gangrene. A proximally pedicled gracilis muscle was used to reconstruct the urethral defect. This healed without stricture or leak. Urethral biopsies showed satisfactory migration of the uroepithelium across the urethral defect.

This study examines the indications for performing the Kleihauer-Betke (KB) test and makes recommendations for its use. Results of 523 KB tests performed during 1993 at our hospital (Cleveland, Ohio) are reviewed in conjunction with surgical pathology reports of placental findings, obstetric records, and toxicology results. We conclude that the KB test should be performed following a positive screening test on all Rh negative mothers of Rh positive infants. Additional indications include cases of maternal trauma, unexplained increased maternal alpha-fetoprotein levels, fetal distress with abnormal heart tracings, intrauterine fetal death, and cases of unexplained neonatal anemia. We note that the KB test should not be performed to detect suspected placental abruption.